Structure analysis suggests Ess1 isomerizes the carboxy-terminal domain of RNA polymerase II via a bivalent anchoring mechanism

Accurate gene transcription in eukaryotes depends on isomerization of serine-proline bonds within the carboxy-terminal domain (CTD) of RNA polymerase II. Isomerization is part of the CTD code that regulates recruitment of proteins required for transcription and co-transcriptional RNA processing. Saccharomyces cerevisiae Ess1 and its human ortholog, Pin1, are prolyl isomerases that engage the long heptad repeat (YSPTSPS)(26) of the CTD by an unknown mechanism. Here, we used an integrative structural approach to decipher Ess1 interactions with the CTD. Ess1 has a rigid linker between its WW and catalytic domains that enforces a distance constraint for bivalent interaction with the ends of long CTD substrates (>= 4-5 heptad repeats). Our binding results suggest that the Ess1 WW domain anchors the proximal end of the CTD substrate during isomerization, and that linker divergence may underlie evolution of substrate specificity. Namitz, Zheng et al. identify a bivalent interaction by the yeast Ess1 with CTD peptides of RNA polymerase II. Their results suggest an anchored mechanism of isomerization, and raise the possibility of eukaryotic parvulin-class prolyl isomerases gaining a broader substrate specificity during evolution, by acquiring a flexible linker that generates a more dynamic binding mode.

Automated summary

Researchers identified a bivalent interaction between yeast Ess1 and CTD peptides of RNA polymerase II, suggesting an anchored mechanism of isomerization. The study raised the possibility of eukaryotic parvulin-class prolyl isomerases gaining broader substrate specificity during evolution by acquiring a flexible linker for a more dynamic binding mode.